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US6759404B2 - Cyclic malonamides as inhibitors of aβ protein production - Google Patents

Cyclic malonamides as inhibitors of aβ protein production Download PDF

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US6759404B2
US6759404B2 US09/825,211 US82521101A US6759404B2 US 6759404 B2 US6759404 B2 US 6759404B2 US 82521101 A US82521101 A US 82521101A US 6759404 B2 US6759404 B2 US 6759404B2
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phenyl
substituted
alkyl
occurrence
independently selected
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US20020103184A1 (en
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Richard E. Olson
Michael G. Yang
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Bristol Myers Squibb Pharma Co
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Bristol Myers Squibb Pharma Co
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Assigned to DUPONT PHARMACEUTICALS COMPANY reassignment DUPONT PHARMACEUTICALS COMPANY ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: OLSON, RICHARD E., YANG, MICHAEL G.
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Priority to US10/746,769 priority patent/US7053081B2/en
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Priority to US11/327,721 priority patent/US7276496B2/en
Priority to US11/841,081 priority patent/US7390896B2/en
Priority to US12/142,145 priority patent/US7528249B2/en
Priority to US12/433,925 priority patent/US20090264419A1/en
Priority to US12/552,652 priority patent/US20100009965A1/en
Priority to US12/603,186 priority patent/US20100041639A1/en
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Definitions

  • This invention relates to novel cyclic malonamides having drug and bio-affecting properties, their pharmaceutical compositions and methods of use. These novel compounds inhibit the processing of amyloid precursor protein and, more specifically, inhibit the production of A ⁇ -peptide, thereby acting to prevent the formation of neurological deposits of amyloid protein. More particularly, the present invention relates to the treatment of neurological disorders related to ⁇ -amyloid production such as Alzheimer's disease and Down's Syndrome.
  • AD Alzheimer's disease
  • AD is a degenerative brain disorder characterized clinically by progressive loss of memory, temporal and local orientation, cognition, reasoning, judgment and emotionally stability.
  • AD is a common cause of progressive dementia in humans and is one of the major causes of death in the United States.
  • AD has been observed in all races and ethnic groups worldwide, and is a major present and future health problem. No treatment that effectively prevents AD or reverses the clinical symptoms and underlying pathophysiology is currently available (for review, Dennis J. Selkoe; Cell Biology of the amyloid (beta)-protein precursor and the mechanism of Alzheimer's disease, Annu Rev Cell Biol, 1994, 10: 373-403).
  • a ⁇ is an internal polypeptide derived from a type 1 integral membrane protein, termed ⁇ amyloid precursor protein (APP).
  • APP ⁇ amyloid precursor protein
  • ⁇ APP is normally produced by many cells both in vivo and in cultured cells, derived from various animals and humans.
  • a ⁇ is derived from cleavage of ⁇ APP by as yet unknown enzyme (protease) system(s), collectively termed secretases.
  • roteolytic activities include ⁇ secretase(s), generating the N-terminus of A ⁇ , ⁇ secretase(s) cleaving around the 16/17 peptide bond in A ⁇ , and ⁇ secretases, generating C-terminal A ⁇ fragments ending at position 38, 39, 40, 42, and 43 or generating C-terminal extended precursors which are subsequently truncated to the above polypeptides.
  • a ⁇ is the major protein found in amyloid plaques.
  • a ⁇ is neurotoxic and may be causally related to neuronal death observed in AD patients.
  • missense DNA mutations at position 717 in the 770 isoform of ⁇ APP can be found in effected members but not unaffected members of several families with a genetically determined (familiar) form of AD.
  • ⁇ APP mutations have been described in familiar forms of AD.
  • similar neuropathological changes have been observed in transgenic animals overexpressing mutant forms of human ⁇ APP.
  • individuals with Down's syndrome have an increased gene dosage of ⁇ APP and develop early-onset AD. Taken together, these observations strongly suggest that A ⁇ depositions may be causally related to the AD.
  • Methods of treatment could target the formation of A ⁇ through the enzymes involved in the proteolytic processing of ⁇ amyloid precursor protein.
  • Compounds that inhibit ⁇ or ⁇ secretase activity could control the production of A ⁇ .
  • compounds that specifically target ⁇ secretases could control the production of A ⁇ .
  • Such inhibition of ⁇ or ⁇ secretases could thereby reduce production of A ⁇ , which, thereby, could reduce or prevent the neurological disorders associated with A ⁇ protein.
  • metalloprotease inhibiting compounds useful for the treatment of diseases associated with excess and/or unwanted matrix metalloprotease activity particularly collagenase and or stromelysin activity.
  • the compounds of the invention are disclosed in PCT publication number WO 95/22966 relating to matrix metalloprotease inhibitors.
  • the compounds of the invention are useful for the treatment of conditions associated with the destruction of cartilage, including corneal ulceration, osteoporosis, periodontitis and cancer.
  • EP 0652009A1 relates to the general formula:
  • lactam ring B is substituted by succinamide and a carbocyclic, aryl, or heteroaryl group.
  • One object of the present invention is to provide novel compounds which are useful as inhibitors of the production of A ⁇ protein or pharmaceutically acceptable salts or prodrugs thereof.
  • It is another object of the present invention to provide pharmaceutical compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of at least one of the compounds of the present invention or a pharmaceutically acceptable salt or prodrug form thereof.
  • It is another object of the present invention to provide a method for treating degenerative neurological disorders comprising administering to a host in need of such treatment a therapeutically effective amount of at least one of the compounds of the present invention or a pharmaceutically acceptable salt or prodrug form thereof.
  • R 3 , R 6 , B, C, W, X, Y, and Z are effective inhibitors of the production of A ⁇ .
  • the present invention provides a novel compound of Formula (I):
  • L is —NR 26 C( ⁇ O)—, —C( ⁇ O)NR 26 —, —NR 26 C( ⁇ O)O—, —OC( ⁇ O)NR 26 , or —NR 26 C ( ⁇ O)NR 26 —;
  • R 3 is —(CR 7 R 7a ) n —R 4 ,
  • n 0, 1, 2, or 3;
  • n 0, 1, 2, or 3;
  • l is 1, 2, or 3;
  • Ring C is a 3 to 8 membered carbocycle
  • carbocycle is saturated or partially saturated
  • the carbocycle contains a heteroatom selected from —O—, —S—, —S( ⁇ O)—, —S( ⁇ O) 2 —, and —N(R 20 )—; and
  • R 4 is H, OH, OR 14a ,
  • 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 4b ;
  • R 4a at each occurrence, is independently selected from H,
  • 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 4b ;
  • R 4b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
  • R 6 is H; C 1 -C 6 alkyl substituted with 0-3 R 6a ; C 3 -C 10 carbocycle substituted with 0-3 R 6b ; or C 6 -C 10 aryl substituted with 0-3 R 6b ;
  • R 6a at each occurrence, is independently selected from H, C 1 -C 6 alkyl, OR 14 , Cl, F, Br, I, ⁇ O, CN, NO 2 , NR 15 R 16 , aryl and CF 3 ;
  • R 6b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, and C 1 -C 4 haloalkoxy;
  • R 7 is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , CF 3 , C 1 -C 4 alkyl, phenyl substituted with 0-5 R 7c ;
  • R 7a is independently selected from H, Cl, F, Br, I, CN, CF 3 , and C 1 -C 4 alkyl;
  • R 7b is independently selected from H and C 1 -C 4 alkyl
  • R 7c is independently selected from H, OH, Cl, F, Br, I, CN, CF 3 , C 1 -C 4 alkoxy, and C 1 -C 4 alkyl;
  • B is a 5 to 10 membered lactam
  • lactam is saturated, partially saturated or unsaturated
  • each additional lactam carbon is substituted with 0-2 R 11 ;
  • the lactam contains an additional heteroatom selected from —O—, —S—, —S( ⁇ O)—, —S( ⁇ O) 2 —, —N ⁇ , —NH—, and —N(R 10 )—;
  • R 10 is H, C( ⁇ O)R 17 , C( ⁇ O)OR 17 , C( ⁇ O)NR 18 R 19 ,
  • R 10a is independently selected from H, C 1 -C 6 alkyl, OR 14 , Cl, F, Br, I, ⁇ O, CN, NO 2 , NR 15 R 16 , CF 3 , aryl substituted with 0-4 R 10b ; C 3 -C 10 carbocycle substituted with 0-3 R 10b , and 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 10b ;
  • R 10b is independently selected from H, OH, C 1 -C 6 alkyl, C 1 -C 4 alkoxy, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
  • R 11 at each occurrence, is independently selected from
  • 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 11b ;
  • R 11a at each occurrence, is independently selected from
  • 5 to 6 membered heterocycle containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R 11b ;
  • R 11b at each occurrence, is independently selected from H,
  • R 11 substituents on adjacent atoms may be combined to form a 5 to 6 membered heteroaryl fused radical, wherein said 5 to 6 membered heteroaryl fused radical comprises 1 or 2 heteroatoms selected from N, O, and S; wherein said 5 to 6 membered heteroaryl fused radical is substituted with 0-3 R 13 ;
  • R 11 substituents on the same or adjacent carbon atoms may be combined to form a C 3 -C 6 carbocycle substituted with 0-3 R 13 ;
  • R 11 substituents on adjacent atoms may be combined to form a benzo fused radical; wherein said benzo fused radical is substituted with 0-4 R 13 ;
  • W is —(CR 8 R 8a ) p —;
  • p 0, 1, 2, 3, or 4;
  • R 8 and R 8a are independently selected from H, F, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl and C 3 -C 8 cycloalkyl;
  • X is a bond
  • R Xb is independently selected from H
  • Y is a bond or —(CR 9 R 9a ) t —V—(CR 9 R 9a ) u —;
  • t 0, 1, 2, or 3;
  • u 0, 1, 2, or 3;
  • R 9 and R 9a are independently selected from H, F, C 1 -C 6 alkyl and C 3 -C 8 cycloalkyl;
  • V is a bond, —C( ⁇ O)—, —O—, —S—, —S( ⁇ O)—, —S( ⁇ O) 2 —, —N(R 19 )—, —C( ⁇ O)NR 19b —, —NR 19b C( ⁇ O)—, —NR 19b S( ⁇ O) 2 —, —S( ⁇ O) 2 NR 19b —, —NR 19b S( ⁇ O)—, —S( ⁇ O)NR 19b —, —C( ⁇ O)O—, or —OC( ⁇ O)—;
  • R 12 at each occurrence, is independently selected from C 6 -C 10 aryl substituted with 0-4 R 12b ;
  • R 12a is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , —C( ⁇ O)NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
  • R 12b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
  • R 13 at each occurrence, is independently selected from H, OH, C 1 -C 6 alkyl, C 1 -C 4 alkoxy, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , and CF 3 ;
  • R 14 is H, phenyl substituted with 0-4 R 14b , benzyl substituted with 0-4 R 14b , C 1 -C 6 alkyl, C 2 -C 6 alkoxyalkyl, or C 3 -C 6 cycloalkyl;
  • R 14a is H, C 6 -C 10 aryl, benzyl, heterocycle, or C 1 -C 4 alkyl;
  • R 14b at each occurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 ,
  • R 15 is independently selected from H, C 1 -C 6 alkyl, aryl-(C 1 -C 6 alkyl)— wherein the aryl is substituted with 0-4 R 15b , (C 1 -C 6 alkyl)-C( ⁇ O)—, and (C 1 -C 6 alkyl)-S( ⁇ O) 2 —;
  • R 15b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 ,
  • R 16 is independently selected from H, C 1 -C 6 alkyl, benzyl, phenethyl,
  • R 17 is H, C 1 -C 6 alkyl, C 2 -C 6 alkoxyalkyl,
  • R 17a is H, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, —OH, F, Cl, Br, I, CF 3 , OCF 3 , SCH 3 , S(O)CH 3 , SO 2 CH 3 , —NH 2 , —N(CH 3 ) 2 , or C 1 -C 4 haloalkyl;
  • R 18 is independently selected from H, C 1 -C 6 alkyl, phenyl, benzyl, phenethyl,
  • R 19 is independently selected from H, OH, C 1 -C 6 alkyl, phenyl, benzyl, phenethyl,
  • R 20 is H, C( ⁇ O)R 17 , C( ⁇ O)OR 17 , C( ⁇ O)NR 18 R 19 ,
  • R 20a is independently selected from H, C 1 -C 6 alkyl, OR 14 , F, ⁇ O, CN, NO 2 , NR 15 R 16 , CF 3 , aryl substituted with 0-4 R 20b , and heterocycle substituted with 0-4 R 20b ;
  • R 20b is independently selected from H, OH, C 1 -C 6 alkyl, C 1 -C 4 alkoxy, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
  • R 21 is independently selected from H, C 1 -C 4 alkoxy, Cl, F, Br, I, ⁇ O, CN, NO 2 , NR 18 R 19 ,
  • R 21a is independently selected from H, C 1 -C 6 alkyl, OR 14 , Cl, F, Br, I, ⁇ O, CN, NO 2 , NR 15 R 16 , CF 3 ;
  • 5 to 6 membered heterocycle containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R 21b ;
  • R 21b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 ,
  • R 21 substituents on adjacent atoms may be combined to form a 5 to 6 membered heteroaryl fused radical, wherein said 5 to 6 membered heteroaryl fused radical comprises 1 or 2 heteroatoms selected from N, O, and S; wherein said 5 to 6 membered heteroaryl fused radical is substituted with 0-3 R 23 ;
  • R 21 substituents on the same or adjacent carbon atoms may be combined to form a C 3 -C 6 carbocycle substituted with 0-3 R 23 ;
  • R 21 substituents on adjacent atoms may be combined to form a benzo fused radical; wherein said benzo fused radical is substituted with 0-4 R 23 ;
  • R 23 is independently selected from H, OH, C 1 -C 6 alkyl, C 1 -C 4 alkoxy, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , and CF 3 ;
  • R 26 is H
  • R 26a is independently selected from H, C 1 -C 6 alkyl, OR 14 , Cl, F, Br, I, ⁇ O, CN, NO 2 , NR 15 R 16 , aryl and CF 3 ; and
  • R 26b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, and C 1 -C 4 haloalkoxy.
  • L is —NR 26 C( ⁇ O)—, —C( ⁇ O)NR 26 —, or —OC( ⁇ O)NR 26 —;
  • R 3 is —(CHR 7 ) n —R 4 ,
  • n 0, 1 or 2;
  • n 0, 1 or 2;
  • Ring C is a 3 to 8 membered carbocycle substituted with 0-4 R 21 ; optionally, the carbocycle contains a heteroatom selected from —O— and —N(R 20 )—;
  • R 4 is H, OH, OR 14a ,
  • 5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R 4b ;
  • R 4a at each occurrence, is independently selected from H,
  • 5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R 4b ;
  • R 4b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 4 alkyl, C 1 -C 3 alkoxy, C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;
  • R 6 is H
  • R 7 at each occurrence, is independently selected from H, OH, F, CF 3 , methyl, and ethyl;
  • Ring B is a 7 membered lactam
  • lactam is saturated, partially saturated or unsaturated
  • each additional lactam carbon is substituted with 0-2 R 11 ;
  • the lactam contains a heteroatom selected from —O—, —S—, —S( ⁇ O)—, —S( ⁇ O) 2 —, —N ⁇ , —NH—, and —N(R 10 )—;
  • R 10 is H, C( ⁇ O)R 17 , C( ⁇ O)OR 17 , C( ⁇ O)NR 18 R 19 ,
  • R 10a at each occurrence, is independently selected from H,
  • R 10b is independently selected from H, OH, C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C, F, Br, I, CN, NO 2 , NR 15 R 16 , and CF 3 ;
  • R 11 at each occurrence, is independently selected from
  • 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 11b ;
  • R 11a is independently selected from H, C 1 -C 6 alkyl, OR 14 , Cl, F, Br, I, ⁇ O, CN, NO 2 , NR 15 R 16 , CF 3 , or phenyl substituted with 0-3 R 11b ;
  • R 11b is independently selected from H, OH, C, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, and C 1 -C 4 haloalkoxy;
  • R 11 substituents on adjacent atoms may be combined to form a benzo fused radical; wherein said benzo fused radical is substituted with 0-2 R 13 ;
  • R 11 substituents on adjacent atoms may be combined to form a 5 to 6 membered heteroaryl fused radical, wherein said 5 to 6 membered heteroaryl fused radical comprises 1 or 2 heteroatoms selected from N, O, and S; wherein said 5 to 6 membered heteroaryl fused radical is substituted with 0-2 R 13 ;
  • R 11 substituents on the same or adjacent carbon atoms may be combined to form a C 3 -C 6 carbocycle substituted with 0-2 R 13 ;
  • W is a bond, —CH 2 —, —CH(CH 3 )—, —CH 2 CH 2 — or —CH(CH 3 )CH 2 —;
  • X is a bond
  • R Xb is independently selected from H, OH, Cl, F, NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 4 alkyl, C 1 -C 3 alkoxy, C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;
  • Y is a bond, —CH 2 —V—, —V—, or —V—CH 2 —;
  • V is a bond, —C( ⁇ O)—, —O—, —S—, —S( ⁇ O)—, —S( ⁇ O) 2 —, —NH—, —N(CH 3 )—, or —N(CH 2 CH 3 )—,
  • Z is H; C 1 -C 6 alkyl; C 2 -C 4 alkenyl; C 2 -C 4 alkynyl;
  • R 12 at each occurrence, is independently selected from
  • R 12b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
  • R 13 at each occurrence, is independently selected from H, OH, C 1 -C 6 alkyl, C 1 -C 4 alkoxy, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , and CF 3 ;
  • R 14 is H, phenyl, benzyl, C 1 -C 4 alkyl, or C 2 -C 4 alkoxyalkyl;
  • R 14a is H, phenyl, benzyl, or C 1 -C 4 alkyl
  • R 15 is independently selected from H, C 1 -C 4 alkyl, benzyl, phenethyl, (C 1 -C 4 alkyl)-C( ⁇ O)—, and (C 1 -C 4 alkyl)-S( ⁇ O) 2 —;
  • R 16 is independently selected from H, OH, C 1 -C 4 alkyl, benzyl, phenethyl, (C 1 -C 4 alkyl)-C( ⁇ O)—, and (C 1 -C 4 alkyl)-S( ⁇ O) 2 —;
  • R 17 is H, methyl, ethyl, propyl, butyl, methoxymethyl,
  • R 17a is H, methyl, methoxy, —OH, F, Cl, CF 3 , or OCF 3 ;
  • R 18 is independently selected from H, methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;
  • R 19 is independently selected from H, methyl, and ethyl
  • R 20 is H or C( ⁇ O)OR 17 ;
  • R 26 is H, methyl, or ethyl.
  • Ring C is selected from:
  • Ring C is substituted with 0-2 R 21 ;
  • Ring B is selected from:
  • L is —NHC( ⁇ O)—, —C( ⁇ O)NH—, or —OC( ⁇ O)NH—;
  • R 3 is R 4 , —CH 2 OR 4 , or —CH 2 CH 2 OR 4 ;
  • R 4 is C 1 -C 6 alkyl substituted with 0-3 R 4a ,
  • R 4a at each occurrence, is independently selected from
  • 5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R 4b ; wherein said 5 to 6 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and tetrazolyl;
  • R 4b is independently selected from H, OH, Cl, F, NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;
  • W is a bond, —CH 2 —, —CH(CH 3 )—, —CH 2 CH 2 — or —CH(CH 3 )CH 2 —;
  • X is a bond, phenyl, C 3 -C 6 cycloalkyl, or 5 to 6 membered heterocycle
  • Y is a bond, —C( ⁇ O)—, —O—, —S—, —S( ⁇ O)—, —S( ⁇ O) 2 —, —NH—, —N(CH 3 )—, or —N(CH 2 CH 3 )—,
  • Z is H; C 1 -C 6 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl,
  • 5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R 12b ; wherein said 5 to 6 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and tetrazolyl;
  • R 12 at each occurrence is independently selected from
  • 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 12b ; wherein said 5 to 6 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and tetrazolyl;
  • R 12b is independently selected from
  • R 13 at each occurrence, is independently selected from H, OH, methyl, ethyl, propyl, butyl, methoxy, ethoxy, Cl, F, Br, CN, NR 15 R 16 , and CF 3 ;
  • R 14 is H, phenyl, benzyl, methyl, ethyl, propyl, or butyl;
  • R 15 is independently selected from H, methyl, ethyl, propyl, and butyl;
  • R 16 at each occurrence is independently selected from H, OH, methyl, ethyl, propyl, butyl, benzyl, phenethyl, methyl-C( ⁇ O)—, ethyl-C( ⁇ O)—, methyl-S( ⁇ O) 2 —, ethyl-S( ⁇ O) 2 —, and propyl-S( ⁇ O) 2 —;
  • R 18 is independently selected from H, methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;
  • R 19 is independently selected from H, methyl, and ethyl
  • R 20 is H.
  • L is —NHC( ⁇ O)—, —C( ⁇ O)NH—, or —OC( ⁇ O)NH—;
  • R 3 is —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 CH(CH 3 ) 2 , —CH 2 (CH 3 ) 2 , —CH(CH 3 )CH 2 CH 3 , —CH 2 CH(CH 3 ) 2 , —CH 2 C(CH 3 ) 3 , —CF 3 , —CH 2 CF 3 , —CH 2 CH 2 CF 3 , —CH 2 CH 2 CH 2 CF 3 , —CH(OH)CH 2 CH(CH 3 ) 2 , —CH(OH)CH(CH 3 ) 2 , —CH(NH 2 )CH 2 CH(CH 3 ) 2 , —CH 2 CH 2 OCH 3 , —CH 2 OCH 2 CH 3 , —CF 2 CH 2 CH(CH 3 ) 2 , —CH(NHCH 3 )CH 2 CH(CH 3 ) 2 ,
  • Ring C is selected from:
  • Ring B is selected from:
  • each benzo fused ring is substituted with 0-1 R 13 ;
  • W is a bond or —CH 2 —
  • X is a bond
  • Y is a bond, —C( ⁇ O)—, —O—, —S—, —S( ⁇ O)—, —S( ⁇ O) 2 —, —NH—, or —N(CH 3 )—,
  • Z is phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 2-Cl-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl, 2,4-diF-phenyl, 2,5-diF-phenyl, 2,6-diF-phenyl, 3,4-diF-phenyl, 3,5-diF-phenyl, 2,3-diCl-phenyl, 2,4-diCl-phenyl, 2,5-diCl-phenyl, 2,6-diCl-phenyl, 3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-4-Cl-phenyl, 3-F-5-Cl-phenyl, 3-Cl-4-F-phenyl, 2-MeO-phenyl, 3-MeO-phenyl, 4-MeO-phenyl, 2-Me-pheny
  • R 10 is H, methyl, ethyl, phenyl, benzyl, phenethyl, 4-F-phenyl, (4-F-phenyl)CH 2 —, (4-F-phenyl)CH 2 CH 2 —, 4-Cl-phenyl, (4-Cl-phenyl)CH 2 —, (4-Cl-phenyl)CH 2 CH 2 —, 4-CH 3 -phenyl, (4-CH 3 -phenyl)CH 2 —, (4-CH 3 -phenyl)CH 2 CH 2 —, 4-CF 3 -phenyl, (4-CF 3 -phenyl)CH 2 —, or (4-CF 3 -phenyl)CH 2 CH 2 —;
  • R 11 is independently selected from H, ⁇ O, methyl, ethyl, phenyl, benzyl, phenethyl, 4-F-phenyl, (4-F-phenyl)CH 2 —, (4-F-phenyl)CH 2 CH 2 —, 3-F-phenyl, (3-F-phenyl)CH 2 —, (3-F-phenyl)CH 2 CH 2 —, 2-F-phenyl, (2-F-phenyl)CH 2 —, (2-F-phenyl)CH 2 CH 2 —, 4-Cl-phenyl, (4-Cl-phenyl)CH 2 —, (4-Cl-phenyl)CH 2 CH 2 —, 3-Cl-phenyl, (3-Cl-phenyl)CH 2 —, (3-Cl-phenyl)CH 2 CH 2 —, 4-CH 3 -phenyl, (4-CH 3 -phenyl)CH 2 —, (4-CH 3 -phenyl)CH
  • R 13 at each occurrence, is independently selected from H, F, Cl, OH, —CH 3 , —CH 2 CH 3 , —OCH 3 , and —CF 3 ;
  • R 20 is H.
  • the present invention provides a compound of Formula (I), wherein:
  • R 3 is —(CR 7 R 7a ) n —R 4 ,
  • n 0, 1, or 2;
  • n 0, 1, or 2;
  • l is 1 or 2;
  • Ring C is a 3 to 8 membered carbocycle substituted with 0-4 R 21 ; optionally, the carbocycle contains a heteroatom selected from —O—, and —N(R 20 )—;
  • R 4 is H, OH, OR 14a ,
  • 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 4b ;
  • R 4a at each occurrence, is independently selected from is H, F, Cl, Br, I, CF 3 ,
  • 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 4b ;
  • R 4b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, and C 1 -C 4 haloalkoxy;
  • R 6 is H, methyl, or ethyl
  • R 7 is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , CF 3 , phenyl and C 1 -C 4 alkyl;
  • R 7a is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , CF 3 , and C 1 -C 4 alkyl;
  • R 7b is independently selected from H, methyl, ethyl, propyl, and butyl;
  • Ring B is a 7 membered lactam
  • lactam is saturated, partially saturated or unsaturated
  • each additional lactam carbon is substituted with 0-2 R 11 ;
  • the lactam contains a heteroatom selected from, —O—, —S—, —S( ⁇ O)—, —S( ⁇ O) 2 —, —N ⁇ , —NH—, and —N(R 10 )—;
  • R 10 is H, C( ⁇ O)R 17 , C( ⁇ O)OR 17 , C( ⁇ O)NR 18 R 19 ,
  • R 10a is independently selected from H, C 1 -C 6 alkyl, OR 14 , Cl, F, Br, I, ⁇ O, CN, NO 2 , NR 15 R 16 , CF 3 , phenyl substituted with 0-4 R 10b ; or 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 10b ;
  • R 10b is independently selected from H, OH, C 1 -C 6 alkyl, C 1 -C 4 alkoxy, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , or CF 3 ;
  • R 11 is independently selected from H, C 1 -C 4 alkoxy, Cl, F, Br, I, ⁇ O, CN, NO 2 , NR 18 R 19 , C( ⁇ O)R 17 , C( ⁇ O)OR 17 , C( ⁇ O)NR 18 R 19 , S( ⁇ O) 2 NR 18 R 19 , CF 3 ;
  • 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 11b ;
  • R 11a is independently selected from H, C 1 -C 6 alkyl, OR 14 , Cl, F, Br, I, ⁇ O, CN, NO 2 , NR 15 R 16 , CF 3 , or phenyl substituted with 0-3 R 11b ;
  • R 11b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, and C 1 -C 4 haloalkoxy;
  • R 11 substituents on adjacent atoms may be combined to form a benzo fused radical; wherein said benzo fused radical is substituted with 0-3 R 13 ;
  • R 11 substituents on adjacent atoms may be combined to form a 5 to 6 membered heteroaryl fused radical, wherein said 5 to 6 membered heteroaryl fused radical comprises 1 or 2 heteroatoms selected from N, O, and S; wherein said 5 to 6 membered heteroaryl fused radical is substituted with 0-3 R 13 ;
  • R 11 substituents on the same or adjacent carbon atoms may be combined to form a C 3 -C 6 carbocycle substituted with 0-3 R 13 ;
  • W is —(CR 8 R 8a ) p —;
  • p 0, 1, or 2;
  • R 8 and R 8a are independently selected from H, F, C 1 -C 3 alkyl, C 2 -C 3 alkenyl, C 2 -C 3 alkynyl and C 3 -C 6 cycloalkyl;
  • X is a bond
  • R Xb is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, and C 1 -C 4 haloalkoxy;
  • Y is a bond or —(CR 9 R 9a ) t —V—(CR 9 R 9a ) u —;
  • t 0, 1, or 2;
  • u 0, 1, or 2;
  • R 9 and R 9a are independently selected from H, F, C 1 -C 4 alkyl or C 3 -C 6 cycloalkyl;
  • V is a bond, —C( ⁇ O)—, —O—, —S—, —S( ⁇ O)—, —S( ⁇ O) 2 —, —N(R 19 )—, —C( ⁇ O)NR 19b —, —NR 19b C( ⁇ O)—, —NR 19b S( ⁇ O) 2 , —S( ⁇ O) 2 NR 19b —, —NR 19b S( ⁇ O)—, or —S( ⁇ O)NR 19b —;
  • R 12a is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, and C 1 -C 4 haloalkoxy;
  • R 13 at each occurrence, is independently selected from H, OH, C 1 -C 6 alkyl, C 1 -C 4 alkoxy, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , and CF 3 ;
  • R 14 is H, phenyl, benzyl, C 1 -C 6 alkyl, or C 2 -C 6 alkoxyalkyl;
  • R 14a is H, phenyl, benzyl, methyl, ethyl, propyl, or butyl;
  • R 15 is independently selected from H, C 1 -C 6 alkyl, benzyl, phenethyl, (C 1 -C 6 alkyl)-C( ⁇ O)—, and (C 1 -C 6 alkyl)-S( ⁇ O) 2 —;
  • R 16 is independently selected from H, OH, C 1 -C 6 alkyl, benzyl, phenethyl, (C 1 -C 6 alkyl)-C( ⁇ O)—, and (C 1 -C 6 alkyl)-S( ⁇ O) 2 —;
  • R 17 is H, C 1 -C 6 alkyl, C 2 -C 6 alkoxyalkyl, aryl substituted by 0-4 R 17a , or —CH 2 -aryl substituted by 0-4 R 17a ;
  • R 17a is H, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, —OH, F, Cl, Br, I, CF 3 , OCF 3 , SCH 3 , S(O)CH 3 , SO 2 CH 3 , —NH 2 , —N(CH 3 ) 2 , or C 1 -C 4 haloalkyl;
  • R 18 is independently selected from H, C 1 -C 6 alkyl, phenyl, benzyl, phenethyl, (C 1 -C 6 alkyl)-C( ⁇ O)—, and (C 1 -C 6 alkyl)-S( ⁇ O) 2 —; and
  • R 19 is independently selected from H, OH, C 1 -C 6 alkyl, phenyl, benzyl, phenethyl, (C 1 -C 6 alkyl)-C( ⁇ O)—, and (C 0 -C 6 alkyl)-S( ⁇ O) 2 —
  • R 20 is H or C( ⁇ O)R 17 ;
  • R 21 is independently selected from
  • R 21a is independently selected from H, C 1 -C 6 alkyl, OR 14 , Cl, F, Br, I, ⁇ O, CN, NO 2 , NR 15 R 16 , CF 3 ;
  • 5 to 6 membered heterocycle containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R 21b ;
  • R 21b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 ,
  • R 21 substituents on the same or adjacent carbon atoms may be combined to form a C 3 -C 6 carbocycle substituted with 0-3 R 23 ;
  • R 21 substituents on adjacent atoms may be combined to form a benzo fused radical; wherein said benzo fused radical is substituted with 0-4 R 23 ;
  • R 23 at each occurrence, is independently selected from
  • L is —NR 26 C( ⁇ O)—, —C( ⁇ O)NR 26 —, —NR 26 C( ⁇ O)O—, —OC( ⁇ O)NR 26 , or —NR 26 C( ⁇ O)NR 26 —;
  • R 3 is —(CR 7 R 7a ) n —R 4 ,
  • n 0, 1 or 2;
  • l is 1 or 2;
  • R 4 is H
  • 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 4b ;
  • R 4a is independently selected from H, OH, F, Cl, Br, I, NR 15 R 16 , CF 3 ,
  • 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 4b ;
  • R 4b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
  • Ring C is a 3-8 membered carbocycle
  • the carbocycle contains a heteroatom selected from —O— and —N(R 20 )—;
  • R 21 substituents on adjacent atoms may be combined to form a benzo fused radical; wherein said benzo fused radical is substituted with 0-4 R 23 ;
  • R 21 substituents on adjacent atoms may be combined to form a 5 to 6 membered heteroaryl fused radical, wherein said 5 to 6 membered heteroaryl fused radical comprises 1 or 2 heteroatoms selected from N, O, and S; wherein said 5 to 6 membered heteroaryl fused radical is substituted with 0-3 R 23 ;
  • R 21 substituents on the same or adjacent carbon atoms may be combined to form a C 3 -C 6 carbocycle substituted with 0-3 R 23 ;
  • R 21 is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , NR 15 R 16 , OR 14a , C 1 -C 4 alkyl, C 2 -C 6 alkenyl, alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—, C 3 -C 6 carbocycle, phenyl, and a 5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur;
  • R 6 is H, methyl, or ethyl
  • R 7 at each occurrence, is independently H or C 1 -C 4 alkyl
  • R 7a at each occurrence, is independently H or C 1 -C 4 alkyl
  • R 7b is H or C 1 -C 4 alkyl
  • Ring B is selected from:
  • R 10 is H, C( ⁇ O)R 17 , C( ⁇ O)OR 17 , C( ⁇ O)NR 18 R 19 ,
  • R 10a is independently selected from H, C 1 -C 6 alkyl, OR 14 , Cl, F, Br, I, ⁇ O, CN, NO 2 , NR 15 R 16 , CF 3 , or aryl substituted with 0-4 R 10b ;
  • R 10b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
  • R 11 at each occurrence, is independently selected from
  • 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 11b ;
  • R 11a is independently selected from H, C 1 -C 6 alkyl, OR 14 , Cl, F, Br, I, ⁇ O, CN, NO 2 , NR 15 R 16 , CF 3 ;
  • 5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R 11b ;
  • R 11b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 ,
  • W is a bond or —(CH 2 ) p —;
  • p 1 or 2;
  • X is a bond
  • R Xb is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 4 alkyl, C 1 -C 3 alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, and C 1 -C 3 halothioalkoxy;
  • Y is a bond, —C( ⁇ O)—, —O—, —S—, —S( ⁇ O)—, —S( ⁇ O) 2 —, —N(R 19 )—, —C( ⁇ O)NR 19b —, —NR 19b C( ⁇ O)—, —NR 19b S—( ⁇ O) 2 —, —S( ⁇ O) 2 NR 19b —, —NR 19b S( ⁇ O)—, —S( ⁇ O)NR 19b —, —C( ⁇ O)O—, or —OC( ⁇ O)—;
  • R 12a is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , —C( ⁇ O)NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 haloalkyl-S—,
  • R 12b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
  • R 13 at each occurrence, is independently selected from H, OH, C 1 -C 6 alkyl, C 1 -C 4 alkoxy, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , and CF 3 ;
  • R 14 is H, phenyl, benzyl, C 1 -C 6 alkyl, C 2 -C 6 alkoxyalkyl, or C 3 -C 6 cycloalkyl;
  • R 14a is H, phenyl, benzyl, or C 1 -C 4 alkyl
  • R 15 is independently selected from H, C 1 -C 6 alkyl, benzyl, phenethyl, (C 1 -C 6 alkyl)-C( ⁇ O)—, and (C 1 -C 6 alkyl)-S( ⁇ O) 2 —;
  • R 16 is independently selected from H, OH, C 1 -C 6 alkyl, benzyl, phenethyl, (C 1 -C 6 alkyl)-C( ⁇ O)—, and (C 1 -C 6 alkyl)-S( ⁇ O) 2 —;
  • R 17 is H, C 1 -C 6 alkyl, C 2 -C 6 alkoxyalkyl, aryl substituted by 0-4 R 17a , or —CH 2 -aryl substituted by 0-4 R 17a ;
  • R 17a is H, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, —OH, F, Cl, Br, I, CF 3 , OCF 3 , SCH 3 , S(O)CH 3 , SO 2 CH 3 , —NH 2 , —N(CH 3 ) 2 , or C 1 -C 4 haloalkyl;
  • R 18 is independently selected from H, C 1 -C 6 alkyl, phenyl, benzyl, phenethyl, (C 1 -C 6 alkyl)-C( ⁇ O)—, and (C 1 -C 6 alkyl)-S( ⁇ O) 2 —;
  • R 19 is independently selected from H, OH, methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;
  • R 19b is independently is H or C 1 -C 4 alkyl
  • R 20 is H, C 1 -C 4 alkyl, or C( ⁇ O)OR 17 ;
  • R 23 is independently selected from H, OH, C 1 -C 6 alkyl, C 1 -C 4 alkoxy, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 1 , and CF 3 ; and
  • R 26 is H or C 1 -C 4 alkyl.
  • L is —NR 26 C( ⁇ O)—, —C( ⁇ O)NR 26 —, —NR 26 C( ⁇ O)O—, —OC( ⁇ O)NR 26 , or —NR 26 C( ⁇ O) NR 26 —;
  • R 3 is —(CHR 7 ) n —R 4 ,
  • n 0, 1 or 2;
  • l is 1 or 2;
  • R 4 is H
  • 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 4b ;
  • R 4a is independently selected from H, OH, F, Cl, Br, I, NR 15 R 16 CF 3 ,
  • 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 4b ;
  • R 4b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
  • Ring C is a 3-8 membered carbocycle
  • the carbocycle contains a heteroatom selected from —O—, and —N(R 20 )—;
  • R 21 substituents on adjacent atoms may be combined to form a benzo fused radical; wherein said benzo fused radical is substituted with 0-4 R 23 ;
  • R 21 substituents on the same or adjacent carbon atoms may be combined to form a C 3 -C 6 carbocycle substituted with 0-3 R 23 ;
  • R 21 at each occurrence, is independently selected from H,
  • R 7 at each occurrence, is independently H, methyl, or ethyl
  • R 7b is H, methyl, or ethyl
  • Ring B is selected from:
  • R 11 at each occurrence, is independently selected from
  • 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 11b ;
  • R 11a at each occurrence, is independently selected from
  • 5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R 11b ;
  • R 11b at each occurrence, is independently selected from H,
  • W is a bond or —(CH 2 ) p —;
  • p 1 or 2;
  • X is a bond; phenyl substituted with 0-2 R Xb ; C 3 -C 6 carbocycle substituted with 0-2 R Xb ; or 5 to 6 membered heterocycle substituted with 0-2 R Xb ;
  • R Xb is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 4 alkyl, C 1 -C 3 alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, and C 1 -C 3 halothioalkoxy;
  • Y is a bond, —C( ⁇ O)—, —O—, —S—, —S( ⁇ O)—, —S( ⁇ O) 2 —, —N(R 19 )—, —C( ⁇ O)NR 19b —, —NR 19b C( ⁇ O)—, —NR 19b S( ⁇ O) 2 —, —S( ⁇ O) 2 NR 19b —, —NR 19b S( ⁇ O)—, —S( ⁇ O)NR 19b —, —C( ⁇ O)O—, or —OC( ⁇ O)—;
  • R 12a at each occurrence, is independently selected from
  • R 12b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
  • R 13 at each occurrence, is independently selected from H, OH, C 1 -C 6 alkyl, C 1 -C 4 alkoxy, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , and CF 3 ;
  • R 14 is H, phenyl, benzyl, C 1 -C 6 alkyl, C 2 -C 6 alkoxyalkyl, or C 3 -C 6 cycloalkyl;
  • R 14a is H, phenyl, benzyl, or C 1 -C 4 alkyl
  • R 15 is independently selected from H, C 1 -C 6 alkyl, benzyl, phenethyl, (C 1 -C 6 alkyl)-C( ⁇ O)—, and (C 1 -C 6 alkyl)-S( ⁇ O) 2 —;
  • R 16 is independently selected from H, OH, C 1 -C 6 alkyl, benzyl, phenethyl, (C 1 -C 6 alkyl)-C( ⁇ O)—, and (C 1 -C 6 alkyl)-S( ⁇ O) 2 —;
  • R 17 is H, C 1 -C 6 alkyl, C 2 -C 6 alkoxyalkyl, aryl substituted by 0-4 R 17a , or —CH 2 -aryl substituted by 0-4 R 17a ;
  • R 17a is H, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, butoxy, —OH, F, Cl, Br, I, CF 3 , OCF 3 , SCH 3 , S(O)CH 3 , SO 2 CH 3 , —NH 2 , —N(CH 3 ) 2 , or C 1 -C 4 haloalkyl;
  • R 18 is independently selected from H, C 1 -C 6 alkyl, phenyl, benzyl, phenethyl, (C 1 -C 6 alkyl)-C ( ⁇ O)—, and (C 1 -C 6 alkyl)-S( ⁇ O) 2 —;
  • R 19 is independently selected from H, OH, methyl, ethyl, propyl, butyl, phenyl, benzyl, phenethyl;
  • R 20 is H, C 1 -C 4 alkyl, or C( ⁇ O)OR 17 ;
  • R 23 is independently selected from H, OH, C 1 -C 6 alkyl, C 1 -C 4 alkoxy, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , and CF 3 ; and
  • R 26 is H or C 1 -C 4 alkyl.
  • L is —NHC( ⁇ O)—, —C( ⁇ O)NH—, or —OC( ⁇ O)NH—;
  • R 3 is —(CH 2 ) n —R 4 ,
  • n 0, 1 or 2;
  • l is 1 or 2;
  • R 4 is C 1 -C 8 alkyl substituted with 0-3 R 4a ,
  • 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 4b ;
  • R 4a at each occurrence, is independently selected from
  • 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 4b ;
  • R 4b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
  • R 7b is H, methyl, or ethyl
  • Ring C is a 3-8 membered carbocycle
  • the carbocycle contains a heteroatom selected from —O—, and —N(R 20 )—;
  • R 21 is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , NR 15 R 16 , OR 14a , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
  • W is a bond, —CH 2 —, —CH 2 CH 2 —;
  • X is a bond
  • R Xb is independently selected from H, OH, Cl, F, NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 4 alkyl, C 1 -C 3 alkoxy, C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;
  • Y is a bond, —C( ⁇ O)—, —O—, —S—, —S( ⁇ O)—, —S( ⁇ O) 2 —, —N(R 19 )—, —C( ⁇ O)NR 19b —, —NR 19b C( ⁇ O)—, —NR 19b S( ⁇ O) 2 —, —S( ⁇ O) 2 NR 19b —, —NR 19b S( ⁇ O)—, —S( ⁇ O)NR 19b —, —C( ⁇ O)O—, or —OC( ⁇ O)—;
  • R 12a at each occurrence, is independently selected from
  • R 12b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
  • R 13 at each occurrence, is independently selected from H, OH, C 1 -C 6 alkyl, C 1 -C 4 alkoxy, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , and CF 3 ;
  • R 14 a is H, phenyl, benzyl, or C 1 -C 4 alkyl
  • R 15 is independently selected from H, C 1 -C 6 alkyl, benzyl, phenethyl, (C 1 -C 4 alkyl)-C( ⁇ O)—, and (C 1 -C 4 alkyl)-S( ⁇ O) 2 —;
  • R 16 is independently selected from H, OH, C 1 -C 6 alkyl, benzyl, phenethyl, (C 1 -C 4 alkyl)-C( ⁇ O)—, and (C 1 -C 4 alkyl)-S( ⁇ O) 2 —; and
  • R 20 is H or C 1 -C 4 alkyl.
  • L is —NHC( ⁇ O)—, —C( ⁇ O)NH—, or —OC( ⁇ O)NH—;
  • R 3 is —R 4 , —CH 2 R 4 , —CH 2 CH 2 R 4 , —CH 2 OR 4 , or —CH 2 CH 2 OR 4 ;
  • R 4 is C 1 -C 6 alkyl substituted with 0-3 R 4a ,
  • 5 to 6 membered heterocycle containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R 4b ;
  • R 4a at each occurrence, is independently selected from H,
  • 5 to 6 membered heterocycle containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R 4b ;
  • R 4b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
  • Ring C is a 3-6 membered carbocycle
  • the carbocycle contains a heteroatom selected from —O—, and —N(R 20 )—;
  • R 21 is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , CF 3 , acetyl, SCH 3 , methyl, ethyl, methoxy, ethoxy, allyl, —OCF 3 , and —SCF 3 ;
  • W is a bond, —CH 2 —, —CH 2 CH 2 —;
  • X is a bond
  • R Xb is selected from H, OH, Cl, F, NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , methyl, ethyl, propyl, methoxy, ethoxy, propoxy, and —OCF 3 ;
  • Y is a bond, —C( ⁇ O)—, —O—, —S—, —S( ⁇ O)—, —S( ⁇ O) 2 —, —NH—, —N(CH 3 )—, or —N(CH 2 CH 3 )—;
  • R 12a at each occurrence, is independently selected from
  • R 12b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
  • R 13 at each occurrence, is independently selected from H, OH, C 1 -C 6 alkyl, C 1 -C 4 alkoxy, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , and CF 3 ;
  • R 15 is independently selected from H, C 1 -C 4 alkyl, and benzyl;
  • R 16 is independently selected from H, OH, methyl, ethyl, propyl, butyl, benzyl, phenethyl, methyl-C( ⁇ O)—, ethyl-C( ⁇ O)—, methyl-S( ⁇ O) 2 —, ethyl-S( ⁇ O) 2 —, and propyl-S( ⁇ O) 2 —; and
  • R 20 is H or C 1 -C 4 alkyl.
  • L is —NHC( ⁇ O)—, —C( ⁇ O)NH—, or —OC( ⁇ O)NH—;
  • R 3 is —R 4 , —CH 2 R 4 , —CH 2 CH 2 R 4 , —CH 2 OR 4 , or —CH 2 CH 2 OR 4 ;
  • R 4 is C 1 -C 6 alkyl substituted with 0-3 R 4a , C 2 -C 6 alkenyl substituted with 0-3 R 4a , or C 2 -C 6 alkynyl substituted with 0-3 R 4a ;
  • R 4a at each occurrence, is independently selected from is
  • 5 to 6 membered heterocycle containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R 4b ; wherein said 5 to 6 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and tetrazolyl;
  • R 4b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
  • Ring C is a 3-6 membered carbocycle selected from:
  • R 21 is selected from H, OH, Cl, F, CN, CF 3 , methyl, ethyl, methoxy, ethoxy, allyl, and —OCF 3 ;
  • W is a bond or —CH 2 —
  • X is a bond, phenyl, C 3 -C 6 cycloalkyl or 5 to 6 membered heterocycle
  • Y is a bond, —C( ⁇ O)—, —O—, —S—, —S( ⁇ O)—, —S( ⁇ O) 2 —, —NH—, —N(CH 3 )—, or —N(CH 2 CH 3 )—;
  • R 12a is independently selected from H, OH, Cl, F, NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;
  • 5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R 12b ;
  • R 12b is independently selected from H, OH, Cl, F, NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;
  • R 13 at each occurrence, is independently selected from H, OH, methyl, ethyl, propyl, butyl, methoxy, ethoxy, Cl, F, Br, CN, NR 15 R 16 , and CF 3 ;
  • R 15 is independently selected from H, methyl, ethyl, propyl, and butyl;
  • R 16 is independently selected from H, OH, methyl, ethyl, propyl, butyl, benzyl, and phenethyl;
  • R 20 is H, methyl, or ethyl.
  • L is —NHC( ⁇ O)—, —C( ⁇ O)NH—, or —OC( ⁇ O)NH—;
  • Ring C is selected from:
  • R 3 is —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 CH(CH 3 ) 2 , —CH 2 (CH 3 ) 2 , —CH(CH 3 )CH 2 CH 3 , —CH 2 CH(CH 3 ) 2 , —CH 2 C(CH 3 ) 3 , —CF 3 , —CH 2 CF 3 , —CH 2 CH 2 CF 3 , —CH 2 CH 2 CH 2 CF 3 , —CH(OH)CH 2 CH(CH 3 ) 2 , —CH(OH)CH(CH 3 ) 2 , —CH(NH 2 )CH 2 CH(CH 3 ) 2 , —CH 2 CH 2 OCH 3 , —CH 2 OCH 2 CH 3 , —CF 2 CH 2 CH(CH 3 ) 2 , —CH (NHCH 3 )CH 2 CH(CH 3 ) 2 ,
  • W is a bond or —CH 2 —
  • X is a bond
  • Y is a bond, —C( ⁇ O)—, —O—, —S—, —S( ⁇ O)—, —S( ⁇ O) 2 —, —NH—, or —N(CH 3 )—,
  • Z is methyl, ethyl, i-propyl, n-propyl, n-butyl, i-butyl, s-butyl, t-butyl, allyl, phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 2-Cl-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl, 2,4-diF-phenyl, 2,5-diF-phenyl, 2,6-diF-phenyl, 3,4-diF-phenyl, 3,5-diF-phenyl, 2,3-diCl-phenyl, 2,4-diCl-phenyl, 2,5-diCl-phenyl, 2,6-diCl-phenyl, 3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-4-Cl-phenyl,
  • R 13 at each occurrence, is independently selected from H, F, Cl, OH, —CH 3 , —CH 2 CH 3 , —OCH 3 , or —CF 3 .
  • R 20 is H, methyl, or ethyl.
  • the present invention provides a compound of Formula (Id) and (Ie)
  • L is —NHC( ⁇ O)—, —C( ⁇ O)NH—, or —OC( ⁇ O)NH—;
  • R 3 is —(CH 2 ) n —R 4 ,
  • n 0, 1 or 2;
  • l is 1 or 2;
  • R 4 is C 1 -C 8 alkyl substituted with 0-3 R 4a ,
  • 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 4b ;
  • R 4a at each occurrence, is independently selected from
  • 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 4b ;
  • R 4b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
  • R 7b is H, methyl, or ethyl
  • Ring C is a 3-8 membered carbocycle
  • the carbocycle contains a heteroatom selected from —O— and —N(R 20 )—;
  • R 21 is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , NR 15 R 16 , OR 14a , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
  • R 11 at each occurrence, is independently selected from
  • 5 to 7 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycle is substituted with 0-3 R 11b ; wherein said 5 to 7 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, homopiperidinyl, and tetrazolyl;
  • R 11a is independently selected from H, C 1 -C 4 alkyl, OR 14 , F, Cl, ⁇ O, NR 15 R 16 , CF 3 , or phenyl substituted with 0-3 R 11b ;
  • R 11b is independently selected from H, OH, Cl, F, NR 15 R 16 , CF 3 , methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;
  • W is a bond, —CH 2 —, —CH 2 CH 2 —;
  • X is a bond
  • R Xb is independently selected from H, OH, Cl, F, NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 4 alkyl, C 1 -C 3 alkoxy, C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;
  • Y is a bond, —C( ⁇ O)—, —O—, —S—, —S( ⁇ O)—, —S( ⁇ O) 2 —,
  • R 12a at each occurrence, is independently selected from
  • R 12b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
  • R 13 at each occurrence, is independently selected from H, OH, C 1 -C 6 alkyl, C 1 -C 4 alkoxy, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , and CF 3 ;
  • R 14 is H, phenyl, benzyl, C 1 -C 6 alkyl, C 2 -C 6 alkoxyalkyl, or C 3 -C 6 cycloalkyl;
  • R 14a is H, phenyl, benzyl, or C 1 -C 4 alkyl
  • R 15 is independently selected from H, C 1 -C 6 alkyl, benzyl, phenethyl, (C 1 -C 6 alkyl)-C( ⁇ O)—, and (C 1 -C 6 alkyl)-S( ⁇ O) 2 —;
  • R 16 is independently selected from H, OH, C 1 -C 6 alkyl, benzyl, phenethyl, (C 1 -C 4 alkyl)-C( ⁇ O)—, and (C 1 -C 4 alkyl)-S( ⁇ O) 2 —;
  • R 18 at each occurrence is independently selected from H, C 1 -C 6 alkyl, phenyl, benzyl, phenethyl, (C 1 -C 6 alkyl)-C( ⁇ O)—, and (C 1 -C 6 alkyl)-S( ⁇ O) 2 —;
  • R 19 is independently selected from H, OH, methyl, ethyl, propyl, butyl, phenyl, benzyl, phenethyl; and
  • R 20 is H or C 1 -C 4 alkyl.
  • the present invention provides a compound of Formula (Id) and (Ie) wherein:
  • L is —NHC( ⁇ O)—, —C( ⁇ O)NH—, or —OC( ⁇ O)NH—;
  • R 3 is —R 4 , —CH 2 R 4 , —CH 2 CH 2 R 4 , —CH 2 OR 4 , or —CH 2 CH 2 OR 4 ;
  • R 4 is C 1 -C 6 alkyl substituted with 0-3 R 4a ,
  • 5 to 6 membered heterocycle containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R 4b ;
  • R 4a at each occurrence, is independently selected from is
  • 5 to 6 membered heterocycle containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R 4b ;
  • R 4b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
  • Ring C is a 3-6 membered carbocycle
  • the carbocycle contains a heteroatom selected from —O— and —N(R 20 )—;
  • R 21 is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , CF 3 , acetyl, SCH 3 , methyl, ethyl, methoxy, ethoxy, allyl, —OCF 3 , and —SCF 3 ;
  • R 11 at each occurrence, is independently selected from
  • 5 to 7 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycle is substituted with 0-3 R 11b ; wherein said 5 to 7 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, homopiperidinyl, and tetrazolyl;
  • R 11a is independently selected from H, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, phenoxy, F, Cl, ⁇ O, NR 15 R 16 , CF 3 , or phenyl substituted with 0-3 R 11b ;
  • R 11b is independently selected from H, OH, Cl, F, NR 15 R 16 , CF 3 , methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;
  • W is a bond, —CH 2 —, —CH 2 CH 2 —;
  • X is a bond
  • R Xb is selected from H, OH, Cl, F, NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , methyl, ethyl, propyl, methoxy, ethoxy, propoxy, and —OCF 3 ;
  • Y is a bond, —C( ⁇ O)—, —O—, —S—, —S( ⁇ O)—, —S ( ⁇ O) 2 —, —NH—, —N(CH 3 )—, or —N(CH 2 CH 3 )—;
  • R 12a at each occurrence, is independently selected from
  • R 12b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
  • R 13 at each occurrence, is independently selected from H, OH, C 1 -C 6 alkyl, C 1 -C 4 alkoxy, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , and CF 3 ;
  • R 14 is H, phenyl, benzyl, C 1 -C 4 alkyl, or C 2 -C 4 alkoxyalkyl;
  • R 15 is independently selected from H, methyl, ethyl, propyl, butyl, benzyl, and phenethyl;
  • R 16 is independently selected from H, OH, methyl, ethyl, propyl, butyl, benzyl, phenethyl, methyl-C( ⁇ O)—, ethyl-C( ⁇ O)—, methyl-S( ⁇ O) 2 —, and ethyl-S( ⁇ O) 2 —;
  • R 18 is independently selected from H, methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;
  • R 19 is independently selected from H, methyl, ethyl, propyl, and butyl;
  • R 20 is H or C 1 -C 4 alkyl.
  • the present invention provides a compound of Formula (Id) and (Ie) wherein:
  • L is —NHC( ⁇ O)—, —C( ⁇ O)NH—, or —OC( ⁇ O)NH—;
  • R 3 is —R 4 , —CH 2 R 4 , —CH 2 CH 2 R 4 , —CH 2 OR 4 , or —CH 2 CH 2 OR 4 ;
  • R 4 is C 1 -C 6 alkyl substituted with 0-3 R 4a ,
  • R 4a at each occurrence, is independently selected from is H, OH, F, Cl, Br, I, NR 15 R 16 , CF 3 ,
  • 5 to 6 membered heterocycle containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R 4b ; wherein said 5 to 6 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, and tetrazolyl;
  • R 4b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
  • Ring C is a 3-6 membered carbocycle selected from:
  • R 21 is selected from H, OH, Cl, F, CN, CF 3 , methyl, ethyl, methoxy, ethoxy, allyl, and —OCF 3 ;
  • R 11 at each occurrence, is independently selected from
  • 5 to 7 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycle is substituted with 0-3 R 11b ; wherein said 5 to 7 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, homopiperidinyl, and tetrazolyl;
  • R 11a at each occurrence, is independently selected from H, methyl, ethyl, propyl, methoxy, ethoxy, propoxy, phenoxy, F, Cl, ⁇ O, NR 15 R 16 , CF 3 , or phenyl substituted with 0-3 R 11b ;
  • R 11b is independently selected from H, OH, Cl, F, NR 15 R 16 , CF 3 , methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;
  • W is a bond or —CH 2 —
  • X is a bond, phenyl, C 3 -C 6 cycloalkyl or 5 to 6 membered heterocycle
  • Y is a bond, —C( ⁇ O)—, —O—, —S—, —S( ⁇ O)—, —S( ⁇ O) 2 —, —NH—, —N(CH 3 )—, or —N(CH 2 CH 3 )—;
  • R 12a is independently selected from H, OH, Cl, F, NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;
  • 5 to 6 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R 12b ;
  • R 12b is independently selected from H, OH, Cl, F, NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;
  • R 13 at each occurrence, is independently selected from H, OH, methyl, ethyl, propyl, butyl, methoxy, ethoxy, Cl, F, Br, CN, NR 15 R 16 , and CF 3 ;
  • R 14 is H, phenyl, benzyl, methyl, ethyl, propyl, or butyl;
  • R 15 is independently selected from H, methyl, ethyl, propyl, and butyl;
  • R 16 is independently selected from H, OH, methyl, ethyl, propyl, butyl, benzyl, and phenethyl.
  • R 18 is independently selected from H, methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl;
  • R 19 is independently selected from H, methyl, ethyl, propyl, and butyl;
  • R 20 is H, methyl, or ethyl.
  • the present invention provides a compound of Formula (Id) and (Ie) wherein:
  • L is —NHC( ⁇ O)—, —C( ⁇ O)NH—, or —OC( ⁇ O)NH—;
  • Ring C is selected from:
  • R 3 is —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 CH(CH 3 ) 2 , —CH 2 (CH 3 ) 2 , —CH(CH 3 )CH 2 CH 3 , —CH 2 CH(CH 3 ) 2 , —CH 2 C(CH 3 ) 3 , —CF 3 , —CH 2 CF 3 , —CH 2 CH 2 CF 3 , —CH 2 CH 2 CH 2 CF 3 , —CH(OH)CH 2 CH(CH 3 ) 2 , —CH(OH)CH(CH 3 ) 2 , —CH(NH 2 )CH 2 CH(CH 3 ) 2 , —CH 2 CH 2 OCH 3 , —CH 2 OCH 2 CH 3 , —CF 2 CH 2 CH(CH 3 ) 2 , —CH(NHCH 3 )CH 2 CH(CH 3 ) 2 ,
  • W is a bond or —CH 2 —
  • X is a bond
  • Y is a bond, —C( ⁇ O)—, —O—, —S—, —S( ⁇ O)—, —S( ⁇ O) 2 —, —NH—, or —N(CH 3 )—,
  • Z is methyl, ethyl, i-propyl, n-propyl, n-butyl, i-butyl, s-butyl, t-butyl, allyl, phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 2-Cl-phenyl, 3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl, 2,4-diF-phenyl, 2,5-diF-phenyl, 2,6-diF-phenyl, 3,4-diF-phenyl, 3,5-diF-phenyl, 2,3-diCl-phenyl, 2,4-diCl-phenyl, 2,5-diCl-phenyl, 2,6-diCl-phenyl, 3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-4-Cl-phenyl,
  • R 11 is independently selected from H, ⁇ O, methyl, ethyl, phenyl, benzyl, phenethyl, 4-F-phenyl, (4-F-phenyl)CH 2 —, (4-F-phenyl)CH 2 CH 2 —, 3-F-phenyl, (3-F-phenyl)CH 2 —, (3-F-phenyl)CH 2 CH 2 —, 2-F-phenyl, (2-F-phenyl)CH 2 —, (2-F-phenyl)CH 2 CH 2 —, 4-Cl-phenyl, (4-Cl-phenyl)CH 2 —, (4-Cl-phenyl)CH 2 CH 2 —, 3-Cl-phenyl, (3-Cl-phenyl)CH 2 —, (3-Cl-phenyl)CH 2 CH 2 —, 4-CH 3 -phenyl, (4-CH 3 -phenyl)CH 2 —, (4-CH 3 -phenyl)CH
  • R 13 at each occurrence, is independently selected from H, F, Cl, OH, —CH 3 , —CH 2 CH 3 , —OCH 3 , or —CF 3 .
  • L is —NHC( ⁇ O)—, —C( ⁇ O)NH—, or —OC( ⁇ O)NH—;
  • R 3 is —(CH 2 ) n —R 4 ,
  • n 0, 1 or 2;
  • l is 1 or 2;
  • R 4 is C 1 -C 8 alkyl substituted with 0-3 R 4a ,
  • 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 4b ;
  • R 4a at each occurrence, is independently selected from
  • 5 to 10 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 10 membered heterocycle is substituted with 0-3 R 4b ;
  • R 4b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
  • R 7b is H, methyl, or ethyl
  • Ring C is a 3-8 membered carbocycle
  • the carbocycle contains a heteroatom selected from —O— and —N(R 20 )—;
  • R 21 is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , NR 15 R 16 , OR 14a , C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
  • R 11 is selected from
  • 5 to 7 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycle is substituted with 0-3 R 11b ; wherein said 5 to 7 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, homopiperidinyl, and tetrazolyl;
  • R 11a is independently selected from H, C 1 -C 4 alkyl, OR 14 , F, Cl, ⁇ O, NR 15 R 16 , CF 3 , or phenyl substituted with 0-3 R 11b ;
  • R 11b is independently selected from H, OH, Cl, F, NR 15 R 16 , CF 3 , methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;
  • W is a bond, —CH 2 —, —CH 2 CH 2 —;
  • X is a bond
  • R Xb is independently selected from H, OH, Cl, F, NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 4 alkyl, C 1 -C 3 alkoxy, C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;
  • Y is a bond, —C( ⁇ O)—, —O—, —S—, —S( ⁇ O)—, —S( ⁇ O) 2 —, —N(R 19 )—, —C( ⁇ O)NR 19b —, —NR 19b C( ⁇ O)—, —NR 19b S( ⁇ O) 2 —, —S( ⁇ O) 2 NR 19b —, —NR 19b S( ⁇ O)—, —S( ⁇ O)NR 19b —, —C( ⁇ O)O—, or —OC( ⁇ O)—;
  • R 12a at each occurrence, is independently selected from
  • R 12b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
  • R 14 is H, phenyl, benzyl, C 1 -C 6 alkyl, C 2 -C 6 alkoxyalkyl, or C 3 -C 6 cycloalkyl;
  • R 14a is H, phenyl, benzyl, or C 1 -C 4 alkyl
  • R 15 is independently selected from H, C 1 -C 6 alkyl, benzyl, phenethyl, (C 1 -C 6 alkyl)-C( ⁇ O)—, and (C 1 -C 6 alkyl)-S( ⁇ O) 2 —;
  • R 16 is independently selected from H, OH, C 1 -C 6 alkyl, benzyl, phenethyl, (C 1 -C 4 alkyl)-C( ⁇ O)—, and (C 1 -C 4 alkyl)-S( ⁇ O) 2 —;
  • R 18 is independently selected from H, C 1 -C 6 alkyl, phenyl, benzyl, phenethyl, (C 1 -C 6 alkyl)-C( ⁇ O)—, and (C 1 -C 6 alkyl)-S( ⁇ O) 2 —;
  • R 19 is independently selected from H, OH, methyl, ethyl, propyl, butyl, phenyl, benzyl, phenethyl; and
  • R 20 is H or C 1 -C 4 alkyl.
  • L is —NHC( ⁇ O)—, —C( ⁇ O)NH—, or —OC( ⁇ O)NH—;
  • R 3 is —R 4 , —CH 2 R 4 , —CH 2 CH 2 R 4 , —CH 2 OR 4 , or —CH 2 CH 2 OR 4 ;
  • R 4 is C 1 -C 6 alkyl substituted with 0-3 R 4a ,
  • 5 to 6 membered heterocycle containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R 4b ;
  • R 4a at each occurrence, is independently selected from is
  • 5 to 6 membered heterocycle containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 6 membered heterocycle is substituted with 0-3 R 4b ;
  • R 4b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;
  • Ring C is a 3-6 membered carbocycle
  • the carbocycle contains a heteroatom selected from —O— and —N(R 20 )—;
  • R 21 is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , CF 3 , acetyl, SCH 3 , methyl, ethyl, methoxy, ethoxy, allyl, —OCF 3 , and —SCF 3 ;
  • R 11 is selected from
  • 5 to 7 membered heterocycle containing 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulphur, wherein said 5 to 7 membered heterocycle is substituted with 0-3 R 11b ; wherein said 5 to 7 membered heterocycle is selected from pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl, thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, homopiperidinyl, and tetrazolyl;
  • R 11a is independently selected from H, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, phenoxy, F, Cl, ⁇ O, NR 15 R 16 , CF 3 , or phenyl substituted with 0-3 R 11b ;
  • R 11b is independently selected from H, OH, Cl, F, NR 15 R 16 , CF 3 , methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C 1 -C 2 haloalkyl, and C 1 -C 2 haloalkoxy;
  • W is a bond, —CH 2 —, —CH 2 CH 2 —;
  • X is a bond
  • R Xb is selected from H, OH, Cl, F, NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , methyl, ethyl, propyl, methoxy, ethoxy, propoxy, and —OCF 3 ;
  • Y is a bond, —C( ⁇ O)—, —O—, —S—, —S( ⁇ O)—, —S( ⁇ O) 2 —, —NH—, —N(CH 3 )—, or —N(CH 2 CH 3 )—;
  • R 12a at each occurrence, is independently selected from
  • R 12b is independently selected from H, OH, Cl, F, Br, I, CN, NO 2 , NR 15 R 16 , CF 3 , acetyl, SCH 3 , S( ⁇ O)CH 3 , S( ⁇ O) 2 CH 3 , C 1 -C 6 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, and C 1 -C 4 haloalkyl-S—;

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US11/327,721 US7276496B2 (en) 2000-04-03 2006-01-06 Cyclic malonamides as inhibitors of Aβ protein protection
US11/841,081 US7390896B2 (en) 2000-04-03 2007-08-20 Cyclic malonamides as inhibitors of Aβ protein production
US12/142,145 US7528249B2 (en) 2000-04-03 2008-06-19 Cyclic malonamides as inhibitors of aβ protein production
US12/433,925 US20090264419A1 (en) 2000-04-03 2009-05-01 CYCLIC MALONAMIDES AS INHIBITORS OF Abeta PROTEIN PRODUCTION
US12/552,652 US20100009965A1 (en) 2000-04-03 2009-09-02 Cyclic malonamides as inhibitors of abeta protein production
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US20050009807A1 (en) 2005-01-13
MXPA02009755A (es) 2003-03-27
CA2404023A1 (fr) 2001-10-11
BR0107532A (pt) 2004-11-03
US7276496B2 (en) 2007-10-02
US20090264419A1 (en) 2009-10-22
US20060135762A1 (en) 2006-06-22
US20080021014A1 (en) 2008-01-24
US7528249B2 (en) 2009-05-05
CN1436175A (zh) 2003-08-13
US20020103184A1 (en) 2002-08-01
JP2003535046A (ja) 2003-11-25
EP1268433A1 (fr) 2003-01-02
US20080275024A1 (en) 2008-11-06
IL151576A0 (en) 2003-04-10
WO2001074783A1 (fr) 2001-10-11
AU2001253090A1 (en) 2001-10-15
US7053081B2 (en) 2006-05-30
US20100009965A1 (en) 2010-01-14
US7390896B2 (en) 2008-06-24

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